To understand the nature of uremia-associated disturbances in protein metabolism, we measured whole body Lucite flux in 9 chronic renal failure patients on three separate occasions: Before dialysis when patients were acidotic, [2] before dialysis with sodium bicarbonate supplement and patients were non-acidotic, and (3] 6-8 weeks following initiation of dialysis treatment when patients were non-acidotic and less uremic. All subjects consumed a constant diet for 6 days during each study period. Leucine flux was measured during primed-constant infusion of 13C-leucine. Plasma 13C leucine and 13C KIC (a keto-isocaproate) were measured by gas chromatography/mass spectrometry and expired 13C02, isotope ratio spectrometry. VCO2 was quantitated by a metabolic gas monitor. Turnover kinetics were calculated using standard equations and data on protein kinetics. Because acidosis increased 13C02 production, 3CO2 recovery was measured separately in 6 different pre-dialysis patients with and without acidosis during primed-constant infusion of NaH13cO3.T he recovery rates of the acidotic and non-acidotic patients were not different, 75% and 76%, respectively. An increase in leucine-protein incorporation rate of 16 umol/kg/hr as listed above is equivalent to a rise in protein synthesis of 44.5 g/day for a 70-kg person. These data indicate that acidosis led to accelerated leucine oxidation. While uremia per se did not increase protein degradation, initiation of dialysis treatment resulted in improved protein anabolism as evidenced by a rise in leucine flux and an increase in protein synthesis. These findings underscore the importance of alkali therapy and the initiation of dialysis in maintaining nutritional status of chronic renal failure patients.